dj-927 as second-line therapy in treating patients with progressive locally advanced or metastatic colorectal adenocarcinoma

Conditions: Colorectal Cancer

Summary: rationale: drugs used in chemotherapy, such as dj-927, work in different ways to stop tumor cells from dividing so they stop growing or die. purpose: this phase ii trial is studying how well dj-927 works as second-line therapy in treating patients with progressive locally advanced or metastatic colorectal adenocarcinoma (cancer).

objectives: primary * determine the objective tumor response rate in patients with progressive locally advanced or metastatic adenocarcinoma of the colon or rectum treated with dj-927 as second-line treatment. secondary * determine the duration of response in patients treated with this drug. * determine the time to tumor progression in patients treated with this drug. * determine the median survival time in patients treated with this drug. * determine the quantitative and qualitative toxic effects of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. outline: this is an open-label, multicenter study. patients are stratified according to prior first-line treatment regimen (irinotecan-containing vs oxaliplatin-containing). patients receive oral dj-927\* on day 1. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. note: \*patients receive 1 of 2 selected doses to confirm the previously established maximum tolerated dose patients are followed every 3 months. projected accrual: a total of 56-62 patients (28-31 per stratum) will be accrued for this study within 12 months.

Eligibility criteria:
disease characteristics: * histologically confirmed adenocarcinoma of the colon or rectum * progressive locally advanced or metastatic disease * received 1 prior irinotecan- or oxaliplatin-containing regimen * at least 1 measurable lesion * target lesion must be outside field of prior radiotherapy * no symptomatic brain metastases patient characteristics: age * 18 and over performance status * ecog 0-2 life expectancy * at least 3 months hematopoietic * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 hepatic * alt and ast ≤ 2.5 times upper limit of normal (uln) (5 times uln if liver metastases are present) * bilirubin ≤ 1.5 times uln renal * creatinine ≤ 1.5 times uln gastrointestinal * no difficulty with swallowing * no malabsorption * no diarrhea (excess of 2-3 stools/day above normal frequency) within the past month * no history of chronic diarrhea other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no concurrent serious infection * no other concurrent severe or uncontrolled underlying medical condition that would preclude study participation * no neuropathy ≥ grade 2 * no history of any severe or life-threatening hypersensitivity reaction * no psychiatric disorder that would preclude study compliance * no other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix prior concurrent therapy: biologic therapy * no concurrent biologic therapy chemotherapy * see disease characteristics * at least 4 weeks since prior myelosuppressive chemotherapy and recovered * no other concurrent chemotherapy endocrine therapy * not specified radiotherapy * see disease characteristics * at least 4 weeks since prior radiotherapy and recovered * no concurrent radiotherapy * localized radiotherapy to non-indicator lesions for pain relief allowed provided other methods of pain control are ineffective surgery * at least 4 weeks since prior major surgery and recovered * no prior major surgery in the stomach or small intestine other * more than 28 days since prior investigational agents (including analgesics and/or antiemetics) * no other concurrent anticancer therapy * no other concurrent cytotoxic therapy * no concurrent grapefruit products

Keywords: adenocarcinoma of the colon adenocarcinoma of the rectum recurrent colon cancer recurrent rectal cancer stage iii colon cancer stage iv colon cancer stage iii rectal cancer stage iv rectal cancer